African Americans (AA) experience disproportionate rates of obesity, hypertension, and diabetes. Of particular interest is the tendency for hypertensive AA to also be obese or diabetic. In response to the frequent clustering of obesity, hypertension, and diabetes in AA, researchers have proposed that these diseases share a common pathophysiologic pathway. Recent evidence suggests that this common link could be dietary calcium. While this project focuses on a common pathophysiologic pathway to explain the prevalence of hypertension with diabetes and obesity in African Americans, there are also psychosocial, behavioral, and environmental factors that influence disease incidence and morbidity. Working with our Community Engagement and Outreach Core we will directly investigate the role of calcium in the management of diabetes, hypertension, and obesity in rural areas of North Carolina. The Outreach Core will investigate non-biological factors such as social interaction (family), diet, and exercise; consequently, this project is expected to enhance a systems-level understanding of the relationship of calcium to these diseases in a community setting with identified health disparities. Therefore, the overarching goal of this proiect is to more fully elucidate the role of Ca2+ regulation in obesity, hypertension, and diabetes in African Americans. To address this goal we designed the following Specific Aims: 1) to determine whether impaired calcium sensing receptor function is associated with obesity, hypertension, and diabetes using animal models; 2); to determine whether decreased dietary, urinary, and serum Ca2+ levels are associated with poor obesity, blood pressure, and diabetes management in rural cohorts of African Americans; and 3) to develop a gene-environment interaction network of the calcium homeostatic pathway in relation to physiological measures of diabetes, obesity and hypertension. The results from these studies will provide information that will help in the development of personalized interventions for the treatment and management of obesity, hypertension, and diabetes, particularly African Americans.